Quantitative Magnetic Resonance Properties of Cerebrospinal Fluid and Brain Health Outcomes in Pediatric Congenital Heart Disease

小儿先天性心脏病脑脊液的定量磁共振特性与脑健康结果

• 批准号: 10535593
• 负责人: Vincent Kyu Lee
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10535593
• 关键词: Adolescent; Adult; Age; Blood Circulation; Brain; Cerebellum; Cerebrospinal Fluid; Characteristics; Child; Childhood; Cognitive; Cognitive deficits; Congenital Heart Defects; Cyanosis; Dementia; Department of Defense; Detection; Development; Diagnosis; Disease; Early Diagnosis; Early Intervention; Education; Elderly; Environment; Executive Dysfunction; Exhibits; Face; Funding; General Population; Goals; Growth; Heart Abnormalities; Hippocampus (Brain); Human; Hypoxia; Image; Imaging Techniques; Impaired cognition; Impairment; Individual; Inflammatory; Intraventricular; Language; Lead; Link; Live Birth; Magnetic Resonance; Magnetic Resonance Imaging; Maintenance; Measurement; Measures; Memory; Multimodal Imaging; Neurobiology; Neurodevelopmental Deficit; Neurons; Neuropsychological Tests; Nutrient; Operative Surgical Procedures; Outcome; Participant; Patients; Pediatric Hospitals; Phase; Physiologic pulse; Play; Production; Property; Proteins; Quality of life; Risk Factors; Role; Severities; Shapes; Signal Transduction; Site; Social Interaction; Structure; Subarachnoid Space; Survival Rate; System; T2 weighted imaging; Techniques; Testing; Thick; Third ventricle structure; United States; United States National Institutes of Health; Variant; autism spectrum disorder; base; brain health; brain parenchyma; cerebrospinal fluid flow; cognitive task; cognitive testing; congenital heart disorder; disorder control; executive function; imaging biomarker; improved; in vivo; lateral ventricle; multimodality; nervous system disorder; neurodevelopment; neuronal growth; older patient; olfactory bulb; pediatric patients; peer; wasting

Project Summary/Abstract Children with congenital heart disease (CHD) are more likely to develop neurodevelopmental deficits than the general population. Due to advances in interventional surgical techniques, survival rates for patients with CHD are high, but they face adverse neurodevelopmental challenges – such as cognitive deficits – and attain lower education and social interaction, leading to reduced quality of life. Despite a multitude of studies examining risk factors for adverse neurodevelopment outcomes in children with CHD, only a small proportion of observed variations in cognitive tests can be attributed to these tested exposures. A larger portion of risk factors that may play critical roles in adverse neurodevelopmental outcomes in children with CHD remains to be discovered. One such risk factor is likely to be alterations in cerebrospinal fluid (CSF) characteristics manifested as alterations in volume and flow dynamics. Recent studies show that normal CSF circulation is necessary for healthy neuronal growth and maintenance of a homeostatic environment for normal neuronal function. Abnormalities in the CSF have been linked to neurological diseases such as autism spectrum disorder in children and dementia in adults. In CHD, abnormal CSF findings, especially increased CSF volume, are frequently observed. Increased CSF volume has been shown to be correlated with brain dysmaturation and poor neurodevelopmental outcomes in young children with CHD. Although in the elderly, there are studies that link decreased CSF flow velocities with cognitive impairment. Currently, CSF flow alterations in children with CHD have yet to be examined in vivo, and the possible link between CSF flow and increased volume to cognitive outcomes remains to be explored. This project aims to examine the relationship between disruption in CSF characteristics and neurodevelopmental deficits in children with CHD. We hypothesize that aberrant CSF characteristics (increased volumes and decreased flow velocity) measured using MRI will be powerful multi-modal imaging predictors for neurodevelopmental outcomes in children with CHD. This project leverages a Department of Defense-funded ongoing study at UPMC Children’s Hospital of Pittsburgh involving children with CHD and age-matched healthy controls who receive MRI imaging as well as neuropsychologic testing – including executive function. In this project, we propose measuring intracranial CSF volume (extra-axial and intra-ventricular volume) using structural MRI (T1 and T2 images) and measuring CSF flow velocity through the Aqueduct Silvius using phase-contrast MRI. These CSF measurements will then be correlated with neuropsychological tests assessing executive function. The results from this proposed project will help determine (1) differences in CSF characteristics between children with CHD and healthy controls and (2) any correlation between CSF characteristics and neurodevelopmental outcomes in CHD. Taken together, we hope to develop useful CSF-based imaging biomarkers to prognosticate poor neurodevelopmental outcomes in pediatric patients with CHD.

项目概要/摘要 患有先天性心脏病 (CHD) 的儿童比正常儿童更容易出现神经发育缺陷 由于介入手术技术的进步，冠心病患者的生存率有所提高。 很高，但他们面临着不利的神经发育挑战——例如认知缺陷——并且得分较低 尽管有大量研究检查了风险，但教育和社交互动仍导致生活质量下降。 CHD 儿童神经发育不良结果的因素，仅观察到一小部分 认知测试的变化可归因于这些测试暴露的大部分风险因素。 在先心病儿童的不良神经发育结果中发挥关键作用仍有待发现。 这种危险因素可能是脑脊液（CSF）特征的改变，表现为 最近的研究表明，正常的脑脊液循环对于健康的神经元是必要的。 脑脊液中正常神经元功能的生长和维持异常。 与神经系统疾病有关，例如儿童自闭症谱系障碍和成人痴呆症。 在 CHD 中，经常观察到脑脊液异常，尤其是脑脊液体积增加。 体积已被证明与大脑发育不良和神经发育不良相关 尽管在老年人中，有研究表明脑脊液流速降低与患有先天性心脏病（CHD）有关。 目前，CHD 儿童的脑脊液流量变化尚未在体内进行检查。 脑脊液流量和体积增加与认知结果之间的可能联系仍有待探索。 该项目旨在研究脑脊液特征破坏与神经发育之间的关系 我们勇敢地面对患有先天性心脏病的儿童的脑脊液特征异常（脑脊液体积增加和脑脊液体积增加）。 使用 MRI 测量的流速降低）将成为强大的多模态成像预测因子 该项目利用了国防部资助的项目。 匹兹堡 UPMC 儿童医院正在进行一项研究，涉及患有先心病的儿童和年龄匹配的健康儿童 接受 MRI 成像以及神经心理学测试（包括执行功能）的对照者。 项目中，我们建议使用结构测量颅内脑脊液体积（轴外和脑室内体积） MRI（T1 和 T2 图像）并使用相差测量通过 Silvius 渡槽的 CSF 流速 然后，这些脑脊液测量结果将与评估执行力的神经心理学测试相关联。 该项目的结果将有助于确定 (1) CSF 特征的差异。 患有 CHD 的儿童与健康对照之间的差异，以及 (2) CSF 特征与健康对照之间的任何相关性 总而言之，我们希望开发出有用的基于脑脊液的成像技术。 预测先心病儿科患者神经发育不良结果的生物标志物。